Angiogenesis is a biological process of supplying new blood vessels to tissue or organ, and more particularly, means the formation of new capillary blood vessels from pre-existing capillary blood vessels, which is a basic process of forming blood vessels in a body after growth. The process of forming new blood vessels is a significantly complicated and delicate procedure, and is briefly described as follows. First, when a stimulus for angiogenesis is transmitted to the pre-existing blood vessels, the vessels are expanded and blood vessel permeability is increased. Second, fibrin is released to the outside of the vessel through the expanded vessel to be deposited in a cytoplasmic matrix around the vessel. Third, enzymes for degrading a basement membrane of pre-existing vessels are activated, the basement membranes are degraded, and endothelial cells are released between the degraded basements to be proliferated in matrix of neighboring cells and migrated. Finally, endothelial cells arranged in a row form shape of a vessel, such that a new blood vessel is generated (Risau, W. (1997) Nature: 386 671-674).
The process of angiogenesis is strictly regulated by various negative and positive regulators (Folkman and Cotran., Int. Rev. Exp. Patho., 16, 207˜248, 1976). When angiogenesis is abnormally regulated, various diseases such as cancer, rheumatoid arthritis, diabetic retinopathy, or the like, occur. Particularly, in the case in which this pathological angiogenesis is generated in retina, the angiogenesis causes retinal edema, retinal or vitreous hemorrhage, and finally traction retinal detachment. In addition, the angiogenesis in the retina becomes a major cause of retinopathy of prematurity (ROP), diabetic retinopathy (DR), and age-related macular degeneration (AMD) (Aiello L P, et al., N. Engl. J. Med., 1994, 331, 1480-1487).
Recently, nanoparticles (NPs) have been widely used for industrial and biomedical objects. Particularly, the nanoparticles have been suggested as a selective drug delivery system (P. S. Ghosh, C. K Kim, G. Han, N. S. Forbes, V. M. Rotello, ACS Nano 2008, 2, 2213.) and a potential antibacterial drug against bacterial infection (K. Y. Yoon, J. H. Byeon, J. H. Park, J. Hwang, Sci. Total. Environ. 2007, 373:572.). In addition, it was reported that gold or silver nanoparticles inhibit the angiogenesis induced by vascular endothelial growth factor (VEGF), and researches into development of an angiogenesis inhibitor using the nanoparticle have been conducted. However, in order to use the nanoparticle in treatment, careful evaluation of toxicity of the nanoparticle and effort to minimize the toxicity are necessarily required. That is, development of a nanoparticle therapeutic agent of excellent effect and low toxicity has been requested.
Therefore, the present inventors discovered that inorganic nanoparticles selected from titanium oxide nanoparticles or silica nanoparticles have anti-angiogenic effect at a concentration at which the nanoparticles do not have the toxicity, and completed the present invention.